DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s arguments and amendments filed on 1/16/2026 have been entered.
Claims 1, 7, 8, 10, 14, 17 and 20 have been amended.
In view of Applicant filing TD’s the ODP rejection are withdrawn.
In view of Applicant’s amendments to the claims the 112(b) rejections are withdrawn.
Claims 1-26 are examined in the instant application.
Allowable Subject Matter
Claims 9, 25 and 26 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-8 and 10-24 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Friedland et al. (US 2017/0314015 A1, published 11/2/2017, filed 9/26/2016).
Regarding claims 1, 7, 8, 14-17, Friedland et al. teach a system for modifying a gene within a genomic region of interest comprising a composition comprising a set of 1-4 gRNAs configured to hybridize to a genomic region of interest, using the gRNAs and a nuclease to generate an edit that modifies the gene, wherein the 1st-3rd gRNAs form complexes with the nuclease and wherein binding sites are at least 30 base pairs from a binding site that is hybridized by another gRNA and each hybridization results in a double strand break (pg. 474 Section V. parags. 1469-1505 and pg. 489 parag. 1700).
Regarding claim 2-4, Friedland teaches that the 1st-3rd gRNA will hybridize to a gene, such as an enhancer (parags. 17 and 34-36).
Regarding claims 5 and 18, Friedland teaches that the composition will comprise a donor polynucleotide (parag. 323).
Regarding claims 6 and 19, Friedland teaches that the donor polynucleotide can comprise a point mutation (pg. 475 parag. 1480) and a tag (pg. 16 parag. 270).
Regarding claim 10, Friedland teaches that the gRNAs can be ribonucleoprotein complexes (pg. 474 parags. 1465-1468).
Regarding claims 11 and 24, Friedland teaches that the nuclease comprises Cas9 (pg. 2 parag. 18).
Regarding claims 12, 13, 22 and 23, Friedland teaches that the gRNA can comprise a 5’ or 3’ modification comprising via phosphorothioate internucleotide linkage a 2’-O-methyl sugar modification (parags. 1845-1857)
Regarding claim 20, Friedland teaches contacting a cell with another set of gRNAs that hybridize to another genomic region of interest which is different (pg. 17 parag. 293 and pg. 476 parags. 1490-1505).
Regarding claim 21, Friedland teaches that the system can comprise a lipid capable of transporting gRNA (parags. 1818-1819 and 1919-1920).
Thus, Friedland clearly anticipates claims 1-24.
Response to Arguments
Applicant’s Arguments
Applicants argue in amendment that Friedland does not show that the target sites of three gRNAs must be at least 20 bp apart. Friedland merely suggests this amount of separation as part of a longer recitation of numerical ranges encompassing gRNAs which are targeting areas 0 nucleotides apart, stating "the gRNAs are configured such that, when hybridized to target nucleic acid, they are separated by 0-50, 0-100, 0-200, at least 10, at least 20, at least 30 or at least 50 nucleotides" (see Friedland page 489, [1700]).
Thus, Friedland does not teach that there would be a gain in editing efficiency by specifically positioning the gRNAs at least 20 bp apart or at least 30 bp apart. The present application provides experimental evidence for this distance between three gRNAs increasing the efficiency of an edit when combined with a double stranded nuclease for gene editing as shown in figure 16, wherein editing efficiency improves at distances of over about 20 bp apart. Friedland does not teach or suggest the specific combination that provided the results claimed in claim 1 and also does not teach or suggest using three gRNAs in combination with only a double stranded break generating nuclease as now claimed in amended claims 10, 16 and 17. Friedland only mentions the use of three gRNAs when using a combination of two of the three gRNAs with a nickase, rather than a nuclease capable of making double stranded breaks. Claims 1, 10, 16, 17, 18, and 20 now all specify the use of a nuclease capable of generating double stranded breaks, which is a key feature of the gene editing mechanism utilized in the present application. For at least these reasons, Friedland does not disclose each and every element of the claims as amended.
Examiner’s Response
While Applicant’s arguments have been fully considered they are not found persuasive. Regarding any efficiencies that the claimed composition may exhibit, this is not found persuasive since none of the rejected claims recite limitations regarding any gain in efficiencies resulting from the arraignment of the gRNA’s. Thus Applicant’s arguments regarding efficiencies are not found persuasive since they are not commensurate in scope with the rejected claimed.
Regarding DSB’s, this is also not found persuasive. Friedland explicitly teaches, as cited in parag. 1501 above, that the break resulting from their claimed composition can be a DSB.
Thus the cited art provides the requisite teachings and motivations to make and use the invention as claimed.
Conclusion
No claims are allowed. Claims, 9, 25 and 26 are free of the prior art.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID A MONTANARI whose telephone number is (571)272-3108. The examiner can normally be reached M-Tr 8-6.
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DAVID A. MONTANARI
Examiner
Art Unit 1632
/ANOOP K SINGH/Primary Examiner, Art Unit 1632
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